Content area
Abstract
Topical zinc applications promote wound healing and epithelialization. "Leaky" MDCKII epithelia exposed to apical ZnCl^sub 2^ (10 mM) showed a time-dependent increase (t ^sub 0.5^ 22.2 ± 2.7 min) of transepithelial resistance (R ^sub t^) from 82.3 ± 2.4 Ω cm^sup 2^ to 1,551 ± 225.6 Ω cm^sup 2^; the increase was dose-dependent, being observed at 3 mM but not at 1 mM. Basal Zn^sup 2+^ applications also increased epithelial resistance (at 10 mM to 323 ± 225.6 Ω cm^sup 2^). The linear current-voltage relationship in control epithelia changed after apical 10 mM ZnCl^sub 2^ to show rectification. Voltage deflections resulting from inward currents showed time-dependent relaxation (basal potential difference (p.d.)-positive), with outward currents being time-independent. Cation selectivity was tested after apical ZnCl^sub 2^ elevated resistance; both the NaCl:mannitol (basal replacement) dilution p.d. and the choline:Na bi-ionic p.d. decreased (P^sub Na^/P^sub Cl^ from 4.9 to 2.3 and P^sub Na^/P^sub choline^ from 3.8 to 2.1, respectively). Transepithelial paracellular basal to apical ^sup 45^Ca fluxes increased approximately twofold when driven by a basal positive Na:NMDG bi-ionic p.d., but with basal 10 mM ZnCl^sub 2^, ^sup 45^Ca fluxes decreased approximately twofold. Neither ZO-1 nor occludin distribution was altered after ~2-h exposure to apical 10 mM ZnCl^sub 2^. However, claudin-2, though present at the tight junction, increased within the cell. Increased epithelial barrier resistance by Zn^sup 2+^ is due to modification of the paracellular pathway, most probably by multiple mechanisms.[PUBLICATION ABSTRACT]